Beta-lactam compounds such as penicillins are the most widely used antibiotics due to their effective inhibition of the transpeptidases required for bacterial cell wall synthesis. Beta-lactamases catalyze β-lactam hydrolysis and are primary mediators of bacterial resistance to these compounds. There are four β-lactamase families, Classes A to D, among which Classes A and C are the most commonly observed in the clinic. CTX-M is a new group of Class A β-lactamases that is particularly effective against the extended spectrum β-lactam antibiotics such as cefotaxime, which itself was developed to counter bacterial resistance to first-generation penicillins and cephalosporins. The widespread emergence of extended spectrum beta-lactamase (ESBL) such as CTX-M will continue to limit treatment options for bacterial infections. Since its discovery in the 1990s, CTX-M has become the most frequently observed ESBL in many regions of the world.
The use of a β-lactamase inhibitor in combination with a β-lactam antibiotic is a well-established strategy to counter resistance. Existing β-lactamase inhibitors (e.g., clavulanic acid) generally also contain a β-lactam ring, making them susceptible to resistance stemming from up-regulation of β-lactamase production, selection for new β-lactamases, and other mechanisms evolved over millions of years' chemical warfare between bacteria and β-lactam producing microorganisms. Thus, there is a need to address these issues.